The present application relates to treatment of tumors and, more particularly, to treatment of tumors with iminosugars.
Melanoma is a malignancy of pigment-producing cells (melanocytes) occurring in skin, eyes, ears, gastrointestinal tract, leptomeninges of the central nervous system and oral and genital mucous membranes. Although melanoma accounts for only 4% of all skin cancers, it causes the greatest number of skin cancer-related deaths worldwide. Despite numerous therapeutic strategies no standard therapy exists for patients with metastatic melanoma. The treatment options include monochemotherapy, see e.g. Chapman, P. B., et al. J. Clin. Oncol. 17, 2745-2751, 1999, O'Reilly, et al. Eur. J. Cancer 29A, 940-942, 1993, Khayat, D., et al. Cancer Invest., 12, 414-420, 1994; polychemotherapeutical approaches, see e.g. DelPrete, S. A., et. al. Cancer Treat. Rep. 12, 1343, 1983; immunomodulatory therapies, such as interferon-α and interleukin-2, see e.g. Richards, J. M., et al., Cancer, 69, 427-429, 1992; as well as vaccination therapy with dendritic cells or genetically modified tumor cells, see e.g. Morton, D. L., Barth, A. Ca. Cancer J. Clin. 46, 225-244, 1996, and biochemotherapy, see e.g. Gonzales Cao, M., et al., Melanoma Res. 16, 59-64, 2006.
Melanoma cells can be highly proliferative and invasive. The specific mechanisms conferring intrinsic and acquired drug resistance in melanoma cells are so far poorly understood and difficult to be controlled. Moreover, classical agents, such as dacarbazine, generally considered the most active agent for treating malignant melanoma and approved by the FDA, is not only ineffective, but can be hazardous and counterproductive, resulting in the selection of more chemoresistant cell lines with enhanced tumorogenic and metastatic potential, see e.g. Lev, D., et al., J. Clin. Oncol. 22, 2092-2100, 2004. Thus, a need exists to develop alternative methods for treatment of melanoma.